Assessment of proliferating cell nuclear antigen and its relationship with proinflammatory cytokines and parameters of disease activity in multiple myeloma patients

Multiple myeloma (MM) is a malignant plasma cell disease. Several proinflammatory cytokines produced by malignant plasma cells and bone marrow (BM) stromal cells are involved in the pathogenesis of the disease. We evaluated serum levels of the proinflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-1α), in MM patients before treatment, and determined its significance in tumor progression. We also analyzed the correlation between measured parameters with proliferating cell nuclear antigen (PCNA). Forty-four MM patients and 20 healthy controls were studied. Serum levels of the proinflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA), whereas PCNA value in the BM was determined by immunohistochemistry staining. The mean concentrations of the measured cytokines were significantly different among the three stages of disease, with higher values in advanced disease stage. Furthermore, patients with MM had significantly higher serum levels of the measured cytokines than in controls. A positive correlation was found between IL-6 with IL-1β, IL-8 and MIP-1α. Similarly, IL-8 and MIP-1α were positively correlated with markers of disease activity such as β2 microglobulin and LDH. The proliferation index, determined by PCNA immunostaining, was higher in advanced disease stage. Furthermore PCNA value correlated significantly with β2 microglobulin, LDH and the levels of the measured cytokines. Our results showed that the proliferative activity, as measured with PCNA, increases in parallel with disease stage. The positive correlation between PCNA and other measured mediators supports the involvement of these factors in the biology of myeloma cell growth and can be used as markers of disease activity and as possible therapeutic targets

Instructional leadership in centralised systems: evidence from Greek high-performing secondary schools

This paper examines the enactment of instructional leadership (IL) in high-performing secondary schools (HPSS), and the relationship between leadership and learning in raising student outcomes and encouraging teachers’ professional learning in the highly centralised context of Greece. It reports part of a comparative research study focused on whether, and to what extent, IL has been embraced by Greek school leaders. The study is exploratory, using a qualitative multiple case design to examine two HPSS in Athens. The research design involved a qualitative approach using several different methods, including semi-structured interviews with school principals, deputy heads, subject teachers and subject advisers, plus observation of leadership practice and meetings and scrutiny of relevant policy documents. The findings show that IL is conceptualised as an informal collaborative leadership practice, interwoven with the official multi-dimension role of Greek principals and their ‘semi-IL’ role. In the absence of official IL ‘actors’, teachers’ leadership has been expanding

Angiogenesis-Related Cytokines, RANKL, and Osteoprotegerin in Multiple Myeloma Patients in relation to Clinical Features and Response to Treatment

An essential cytokine system for the osteoclast biology in multiple myeloma (MM) consists of the receptor of activator of NF-κB ligand (RANKL), its receptor (RANK), and the soluble decoy receptor, osteoprotegerin (OPG). Myeloma cells cause imbalance in OPG/RANKL interactions. We measured serum levels of OPG, soluble (s) RANKL, sRANKL/OPG ratio, markers of disease activity [LDH, CRP, interleukin-6 (IL-6), β2-microglobulin (B2M)], and angiogenic factors [hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], in 54 newly diagnosed MM patients and in 25 of them in plateau phase. All the above values were higher in MM patients compared to controls and decreased in plateau phase. sRANKL and RANKL/OPG were higher with advancing disease stage and skeletal grade. Significant correlations were found among RANKL and RANKL/OPG with HGF, LDH, VEGF, IL-6, and B2M. In conclusion, RANKL and OPG play significant roles in MM pathophysiology, as regulators of bone turnover and mediators of angiogenesis

Autoimmune cytopenias developing late post alemtuzumab-based allogeneic stem cell transplantation: presentation of short case series from a transplant center

Stem cell transplantation remains the curative option for many patients with hematological malignancies. The long-term effects of these treatments on the patients and their immune systems have been extensively investigated, but there remains a paucity of data regarding autoimmune manifestations post-transplant, although these effects are well recognized. Herein we present the clinical picture and therapeutic approach in three patients (cases 1–3), with varied presentations of autoimmune disease post-transplant. Case 1 exhibited autoimmune hemolytic anemia and other autoimmune manifestations (serositis, thyroiditis), that were probably linked to graft versus relapsed leukemia effect. Cases 2 and 3 had pure red white cell aplasia and pure red cell aplasia, respectively, which were associated with hyperglobulinemia and a clonal T cell expansion

COVID‐19 in bone marrow transplant recipients : reflecting on a single centre experience

Covid-19 disease is caused by a novel SARS-CoV-2 virus and has been declared a pandemic on the 9 of March by WHO. Hallmark of COVID-19 management is supportive care and there is still no convincing evidence on a treatment which will reduce mortality. Severe COVID-19 associated sepsis characterized by acute respiratory distress syndrome (ARDS), secondary bacterial pneumonias thrombotic complications, myocarditis, and gastrointestinal involvement are more prevalent in those with comorbidities such as hypertension, diabetes, cardiac disease, cancer and age>70 years (Liang et al; 2020, Guan et al; 2019)

First case of near haploid philadelphia negative B-Cell acute lymphoblastic leukaemia relapsing as acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation

Herein we present a female patient aged 61 with Philadelphia negative acute lymphoblastic leukaemia demonstrating near haploid karyotype and abnormal TP53 expression at diagnosis, who relapsed with lineage switch as Acute Monocytic Leukemia post allogeneic stem cell transplantation. Molecular analysis established that both neoplasms were derived from the same founder clone. The leukemic lineage switch phenomenon has recently re-attracted interest as mechanism of leukemic evasion post treatment with chimeric antigen receptor T-cells but there is paucity of data on its presence post allograft or following novel antibody treatments such as Inotuzumab Ozogamicin or Blinatumomab. Our proposition for cancer research is that near haploidy in ALL could be linked to leukemic stem cell plasticity evading stem cell transplantation and other immunotherapy approaches

Management of allogeneic stem cell transplantation for high-risk AML following SARS-CoV-2 associated pancytopenia with marked bone marrow biopsy alterations

The present study describes a patient aged 70 with very high-risk AML who successfully received a nonmyeloablative matched unrelated donor allograft shortly following SARS-CoV-2 infection, which manifested with mild cough, interstitial abnormalities on chest CT, and pancytopenia with profound bone marrow biopsy histological alterations. In parallel, our study provides bone marrow biopsy data in a series of contemporary patients with serious haematological diseases who had a bone marrow biopsy performed within two weeks of PCR confirmation of SARS-CoV-2 infection. This study is notable because there are no published data describing the bone marrow biopsy changes observed in patients with haematological malignancies and SARS-CoV-2 infection. Finally, it is suggested that nonmyeloablative hematopoietic stem cell transplantation for very high-risk haematological malignancies can be successfully performed following recovery from SARS-CoV-2 infection